Neuropsychiatric Symptoms and Microglial Activation in Patients with Alzheimer Disease

Key Points Question Is microglial activation, a proxy for neuroinflammation, associated with neuropsychiatric symptoms in patients with Alzheimer disease? Findings In this cross-sectional study including 109 individuals, levels of microglial activation were associated with neuropsychiatric symptoms in individuals across the Alzheimer disease continuum. Among the neuropsychiatric symptoms, irritability was the most closely associated with the presence of activated microglia. Meaning In this study, the abnormality of microglial activation biomarkers was associated with neuropsychiatric symptoms in patients with Alzheimer disease.

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PET images were corrected for motion, dead time, decay, and scattered and random coincidences, and were registered to the native T1-weighted MRI, which was registered to the ADNI space.PET images were spatially smoothed to an 8-mm full-width at half maximum resolution.

eAppendix. Detailed Imaging Methods eFigure 1 .
Study Participant Flowchart eFigure 2. Frequency of NPI-Q Severity and Distress Scores eFigure 3. Microglial Activation and the Agitation and Frontal NPI-Q Subscales eTable 1. TSPO-PET β-Estimate and Associated Confidence Interval, T-Values, and Adjusted P-Values From the Significant Region-Wise Associations eTable 2. Microglial Activation and Neuropsychiatric Dysfunction eTable 3. Microglial Activation and Neuropsychiatric Dysfunction Using a Censored Regression Model eTable 4. TSPO-PET β-Estimate, Confidence Interval, T-Value, P-Value, and the Magnitude of Change of Each NPI-Q Severity Domain When Applying the Leave-One-Out Technique eTable 5. TSPO-PET β-Estimate, Confidence Interval, T-Value, P Value, and the Magnitude of Change of Each NPI-Q Distress Domain When Applying the Leave-One-Out Technique eReferences.

eFigure 2 .
Frequency of NPI-Q Severity and Distress Scores (A) Bars show the frequency of NPI-Q severity scores in Aβ negative and positive groups.(B) Bars show the frequency of NPI-Q distress scores in Aβ negative and positive groups eFigure 3. Microglial Activation and the Agitation and Frontal NPI-Q Subscales We grouped the NPI-Q in 4 subscales as described in previous studies 4 : agitation (agitation, aberrant motor behavior, irritability, nighttime disturbances), frontal (appetite abnormalities, apathy, disinhibition, elation), mood (depression, anxiety), and psychosis (delusion, hallucinations).To examine the association between microglial activation and NPI-Q subscales, we assessed the sum of each of these 4 subscales as a function of regional TSPO-PET SUVR adjusting for age, sex, and cognitive status.Our results show that microglial activation is associated with the agitation ( = 5.03, C.I = 1.73 -8.33, P = 0.003, R 2 = 0.14) and the frontal ( = 2.60, C.I = 0.37 -4.84, P = 0.02, R 2 = 0.22), but not with the psychosis or the mood subscales.© 2023 Aguzzoli CS et al.JAMA Network Open.
eTable 1. TSPO-PET β-Estimate and Associated Confidence Interval, T-Values, and Adjusted P-Values From the Significant Region-Wise Associations Change of Each NPI-Q Severity Domain When Applying the Leave-One-Out Technique * Adjusted for multiple comparisons with false discovery rate © 2023 Aguzzoli CS et al.JAMA Network Open.Model: [NPI-Q severity score (removing one domain)] ~ TSPO-PET + sex + age + cognitive status